title: RNA sequencing-based identification of aberrant imprinting in cloned mice.
abstract: Animals cloned by somatic cell nuclear transfer (SCNT) provide a unique model for understanding the mechanisms of nuclear epigenetic reprogramming to a state of totipotency. Though many phenotypic abnormalities have been demonstrated in cloned animals, the underlying mechanisms are not well understood. In this study, we performed transcriptome-wide allelic expression analyses in brain and placental tissues of cloned mice. We found that Gab1, Sfmbt2 and Slc38a4 showed loss of imprinting in all cloned mice analyzed, which might be involved in placentomegaly of cloned mice. These three genes did not require de novo DNA methylation in growing oocytes for the establishment of imprinting, implying the involvement of a de novo DNA methylation-independent mechanism. Loss of Dlk1-Dio3 imprinting was also observed in nearly half of cloned mouse embryos and showed a strong correlation with embryonic lethality. Our findings are essential to understand the underlying mechanisms of developmental abnormalities of cloned animals. We also emphasize that particular attention should be paid to specific imprinted genes for therapeutic and agricultural applications of SCNT.
authors.affiliation: Department of Informative Genetics, Environment and Genome Research Center.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okae
authors.forename: Shogo
authors.initials: S
authors.lastname: Matoba
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagashima
authors.forename: Eiji
authors.initials: E
authors.lastname: Mizutani
authors.forename: Kimiko
authors.initials: K
authors.lastname: Inoue
authors.forename: Narumi
authors.initials: N
authors.lastname: Ogonuki
authors.forename: Hatsune
authors.initials: H
authors.lastname: Chiba
authors.forename: Ryo
authors.initials: R
authors.lastname: Funayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Arima
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D026924:Amino Acid Transport System A / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D019976:Cloning, Organism; D005260:Female; D018392:Genomic Imprinting; D007453:Iodide Peroxidase / Q000235:genetics; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D012097:Repressor Proteins; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D026924:Amino Acid Transport System A; C490897:Gab1 protein, mouse; D010750:Phosphoproteins; D012097:Repressor Proteins; C527638:Sfmbt2 protein, mouse; C420522:Slc38a4 protein, mouse; D014157:Transcription Factors; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase